title: Differential and synergistic effects of mechanical stimulation and growth factor presentation on vascular wall function.
abstract: We investigated the hypothesis that immobilizing TGF-β1 within fibrin hydrogels may act in synergy with cyclic mechanical stimulation to enhance the properties of vascular grafts. To this end, we engineered a fusion TGF-β1 protein that can covalently anchor to fibrin during polymerization upon the action of factor XIII. We also developed a 24-well based bioreactor in which vascular constructs can be mechanically stimulated by distending the silastic mandrel in the middle of each well. TGF-β1 was either conjugated to fibrin or supplied in the culture medium and the fibrin-based constructs were cultured statically for a week followed by cyclic distention for another week. The tissues were examined for myogenic differentiation, vascular reactivity, mechanical properties and ECM content. Our results showed that some aspects of vascular function were differentially affected by growth factor presentation vs. pulsatile force application, while others were synergistically enhanced by both. Overall, this two-prong biomimetic approach improved ECM secretion, vascular reactivity and mechanical properties of vascular constructs. These findings may be applied in other tissue engineering applications such as cartilage, tendon or cardiac regeneration where growth factors TGF-β1 and mechano-stimulation play critical roles.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, NY 14260-4200, USA.
authors.forename: Mao-Shih
authors.initials: MS
authors.lastname: Liang
authors.forename: Maxwell
authors.initials: M
authors.lastname: Koobatian
authors.forename: Pedro
authors.initials: P
authors.lastname: Lei
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Swartz
authors.forename: Stelios T
authors.initials: ST
authors.lastname: Andreadis
mesh_terms: D001807:Blood Vessel Prosthesis; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology; D007231:Infant, Newborn; D008297:Male; D018995:Myosin Heavy Chains / Q000378:metabolism; D013314:Stress, Mechanical; D023822:Tissue Engineering; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D055767:Immobilized Proteins; D053773:Transforming Growth Factor beta1; D018995:Myosin Heavy Chains
keywords: Fibrin hydrogels; Growth factor presentation; Mechanical stimulation; Vascular contractility; Vascular tissue engineering